Clinical outcomes of patients with primary refractory metastatic renal cell carcinoma receiving second-line (2L) therapies: An International Metastatic Database Consortium (IMDC) study.
Bibliographic record
Abstract
4555 Background: A subset of patients (pts) with metastatic renal cell carcinoma (mRCC) receiving contemporary first line (1L) immune checkpoint inhibitor (ICI) combinations are considered to be primary refractory. The optimal sequence therapy for this patient population is not well established. Herein, we report practice patterns and clinical outcomes of second line (2L) therapy in pts with primary refractory mRCC. Methods: Data from pts with primary refractory mRCC to 1L ICI and who received 2L therapy were collected through the IMDC. Patients with primary refractory RCC were defined as patients who experienced progressive disease (PD) as best response per RECIST 1.1 criteria. Overall survival (OS) and time to treatment failure (TTF) were calculated from initiation of 2L therapy; their distributions were estimated by the Kaplan Meier methodology. Results: In total, 494 pts had primary progression on 1L ICI, of which 356 (72%) went on to receive subsequent 2L therapy. The most common regimens in the 2L setting included: cabozantinib (n = 137; 38%); sunitinib (n = 115; 32%), and pazopanib (n = 37; 10%). 22% of patients had IMDC poor risk at initiation of 2L. Median follow-up from 2L initiation was 18.8 months. Median OS was 14.5 months, and the median TTF was 5.4 months for the whole cohort. The median OS was 14.4 months (95% CI 11 – 21.4) for cabozantinib, 10.7 months (95% CI 7 -16.6) for sunitinib, and 15.3 months (95% CI 9 – 46) for pazopanib. The median TTF was 4.5 months (95% CI 3.7 -5.6) for cabozantinib, 3.1 months (95% CI 2.8 – 4.4) for sunitinib, and 2.8 months (95% CI 1.7 – 3.6) for pazopanib. The ORR was 20% for pts receiving cabozantinib, 10% for pts receiving sunitinib, and 16% for patients receiving pazopanib. For pts treated with 2L cabozantinib, 84 (61%) had prior dual ICI and 53 (39%) had prior ICI + VEGF. By contrast, for patients treated with sunitinib or pazopanib, the majority (96% and 95%, respectively) had prior dual ICI as 1L. Conclusions: To our knowledge, this is the first initiative to report practice patterns and outcomes of subsequent 2L therapies in patients with primary refractory mRCC to contemporary 1L ICI combinations. Cabozantinib was the most frequently used regimen in this patient population and demonstrated favorable clinical outcomes compared to sunitinib or pazopanib. Biomarker evaluation is needed to explore the mechanism of primary resistance and novel therapeutic strategies for this group. Outcomes of patients with primary refractory mRCC receiving 2L therapies. Treatment Arm N Median OS, months (95% CI) Median TTF, months (95% CI) ORR, % 2L Cabozantinib (1L dual ICI) 84 15 (11 – 26.2) 4.2 (3.4 – 6.6) 20 2L Cabozantinib (1L ICI + VEGF) 53 13.5 (9.8 – NR) 4.8 (3.6 – 5.9) 20 2L Sunitinib 115 10.7 (7 – 16.6) 3.1 (2.8 - 4.4) 10 2L Pazopanib 37 15.3 (9 – 46) 2.8 (1.7 – 3.6) 16
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.001 | 0.002 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".